Consumer medicine information

IMIGRAN FDT tablets [7935]

Sumatriptan

BRAND INFORMATION

Brand name

Imigran FDT (Fast disintegrating tablets)

Active ingredient

Sumatriptan

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using IMIGRAN FDT tablets [7935].

What is in this leaflet?

Please read this leaflet carefully before you start taking Imigran FDT tablets.

This leaflet answers some common questions about Imigran FDT. It does not contain all of the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the expected benefits of you taking Imigran FDT against the risks this medicine could have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine.

You may need to read it again.

What is Imigran FDT used for?

Imigran FDT contains the active ingredient sumatriptan succinate. This medicine belongs to a group of drugs called serotonin agonists.

Imigran FDT is used to relieve a migraine attack. It should not be used to prevent migraine attacks from occurring. Imigran FDT may be used for migraine headaches with or without what is known as 'aura'.

It is thought that migraine headache is due to widening of certain blood vessels in the head.

Imigran FDT works by making those vessels normal again and eases the symptoms of migraine.

Your Imigran FDT does not work in other types of headache which are not a migraine.

Imigran FDT is not addictive.

Before you take Imigran FDT

Do not take if:

You must not take Imigran FDT if:

  • you have ever had an allergic reaction to sumatriptan succinate (See “Side-Effects”) or any of the ingredients listed toward the end of this leaflet. (See “Ingredients”).
  • you have or have had:
    - heart disease or heart attack
    - shortness of breath, pain or tightness in the chest, jaw or upper arm
    - peripheral vascular disease (pain in the back of the legs) or are prone to cold, tingling or numb hands and feet
    - Prinzmetal's angina (an uncommon form of angina where pain is experienced at rest rather than during activity)
    - angina
    - high blood pressure
    - stroke
    - severe liver disease.
  • you have taken any other medicines for migranine in the last 24 hours, such as:
    - ergotamine (eg Cafergot)
    - dihydroergotamine (eg Dihydergot)
    - methysergide (eg Deseril)
    - naratriptan (eg Naramig)
    - zolmitriptan (eg Zomig).
  • you have taken any of these medicines in the last two weeks:
    - Monoamine oxidase inhibitors (MAOIs), a type of medicine used for depression.
    - SSRIs (Selective Serotonin Reuptake Inhibitors) or SNRIs (Serotonin-Noradrenaline Reuptake Inhibitors) used to treat depression.
  • the expiry date (EXP) printed on the pack has passed.
  • the packaging is torn or shows signs of tampering

Tell your doctor if:

You must tell your doctor if:

  • you are allergic to foods, dyes, preservatives or any other medicines, including any that contain sulphur (eg sulphonamide antibiotics)
  • you are taking or have taken any other medicines in the last two weeks, including medicines you buy without a prescription, particularly herbal preparations containing St John's Wort and medicines prescribed for depression
  • you are breastfeeding, pregnant or trying to become pregnant.
  • you have or have had medical conditions like:
    - liver or kidney problems
    - heart problems. Risk factors including high blood pressure, even if it is under control, high blood cholesterol levels, a family history of heart problems, obesity, diabetes, you are male and over 40 years of age, you are female and have undergone menopause or you smoke
    - epilepsy seizures or fits, or been told that you are prone to this problem
    - stroke
  • you are under 18 or over 65 years of age.
  • you think that this headache is different and worse than your usual migraine.
  • you have difficulty moving one side of your body when you have the migraine headache.

How do I take Imigran FDT?

Take your medicine as your doctor has told you. The label on the pack will tell you how many tablets to take and how often you should take them. If you do not understand what you should do, ask your doctor or pharmacist.

How much to take

The recommended starting dose for adults aged 18 to 65 is 50 mg, however you may need to have your dose of Imigran FDT increased to 100 mg. Your doctor will tell you which dose is right for you.

If the first Imigran FDT helps your migraine, but the migraine comes back later, you may take another Imigran FDT. Do not take more than 300 mg of Imigran FDT in any twenty-four hour period. Six pink (50 mg strength) or three white (100 mg strength) FDT contain 300 mg.

Do not take more Imigran FDT , or any other form of Imigran if the first dose has not provided any relief from your symptoms. You may take your usual headache relief medication provided it does not contain ergotamine or methysergide. If you are not sure what to do, ask your doctor or pharmacist.

If your migraine is not relieved by Imigran, you may use Imigran FDT on another occasion to treat another migraine attack. Provided there are no side effects, you can use Imigran FDT to treat at least three separate migraine attacks before you and your doctor decide this medicine is ineffective for you.

How to take it

Imigran FDT should be swallowed with a drink of water. Do not crush or chew the tablet as it has a bitter taste.

When to take it

It is best to take your Imigran FDT -

  1. when the migraine headache begins; or
  2. when other symptoms of the migraine begin, such as nausea (feeling sick), vomiting or your eyes becoming sensitive to light.

If you take your tablet later during the migraine attack it will still work for you. Do not take your Imigran FDTbefore the above symptoms occur.

What do I do if I take too much? (Overdose)

Immediately telephone your doctor or Poisons Information Centre (telephone 131126) for advice, if you think you or anyone else may have taken too many Imigran FDT, even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

If you are not sure what to do, contact your doctor or pharmacist.

While you are taking Imigran FDT

Things you must do

Tell your doctor if, for any reason, you have not taken your medicine exactly as directed.

Otherwise, your doctor may think that it is not working and change your treatment unnecessarily.

Tell your doctor or pharmacist that you are taking Imigran FDT if you are about to be started on any new medicines.

Things you must not do

Do not give this medicine to anyone else, even if their symptoms seem similar to yours.

Things to be careful of

As with many other medicines, Imigran FDT may cause drowsiness in some people.

Be careful driving or operating machinery until you know how Imigran FDT affect you.

If you use Imigran FDT too often, it may make your headache worse. If this happens, your doctor may tell you to stop taking Imigran FDT.

What are the side effects?

Check with your doctor as soon as possible if you think you are experiencing any side effects or allergic reactions due to taking Imigran FDT, even if the problem is not listed below.

Like other medicines, Imigran FDT can cause some side effects. If they occur, they are most likely to be minor and temporary. However, some may be serious and need medical attention.

Tell your doctor if you experienceany of the following after taking Imigran FDT:

  • pain, tingling, heat or flushing in any part of the body
  • feeling of sleepiness, dizziness or tiredness
  • nausea (feeling sick) or vomiting.
  • a change in blood pressure.
  • feeling of faintness.
  • problems with your eyesight.
  • pain in the lower tummy and bloody diarrhoea (ischaemic colitis).
  • shaking or tremors,
  • uncontrolled movements,
  • shortness of breath.

Tell your doctor immediately, or seek urgent medical attention, and do not take any more Imigran FDT if you:

  • feel heaviness, pressure or tightness in any part of the body including the chest or throat.
  • feel irregular heart beats.
  • have a fit or convulsion.
  • have wheezing, swelling of the lips/mouth, difficulty in breathing, hay fever, lumpy rash ("hives") or fainting. These could be a symptom of an allergic reaction.
  • have persistent purple discolouration and/or pain in the fingers, toes, ears, nose or jaw in response to cold.

These side effects are likely to be serious. Stop taking Imigran FDT and seek medical attention straight away.

This is not a complete list of all possible side effects. Others may occur in some people and there may be some side effects not yet known.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

How do I store Imigran FDT?

Keep this medicine where children cannot reach it, such as in a locked cupboard.

Keep Imigran FDT in the blister pack in a cool, dry place where it stays below 30°C.

Do not leave them in a car, on a window sill or in a bathroom.

Keep Imigran FDT in their pack until time to take.

Return any unused or expired medicine to your pharmacist.

Product description

What Imigran FDT look like

Imigran FDT comes in two strengths:

  • Imigran FDT 100 mg are white, triangular shaped, biconvex tablets debossed with ‘GS YE7’ on one face and ‘100’ on the other. A box contains 2 tablets.
  • Imigran FDT 50 mg are pink, triangular shaped, biconvex tablets debossed with ‘GS 1YM’ on one face and ‘50’ on the other. A box contains either 2 or 4 tablets.

Imigran FDT have a film coating to protect the tablet and this gives the colour.

Ingredients

Each Imigran FDT tablet contains the active ingredient sumatriptan (present as sumatriptan succinate) 50mg or 100mg.

Imigran FDT also contains: calcium hydrogen phosphate anhydrous, cellulose – microcrystalline, sodium bicarbonate, croscarmellose sodium and magnesium stearate.

  • Imigran FDT 100 mg are coated with Opadry white OY-S-7322.
  • Imigran FDT 50 mg are coated with Opadry YS-1-1441-G.

Supplier

Your Imigran FDT are supplied by:
Aspen Pharmacare Australia Pty Ltd
34-36 Chandos Street
St Leonards, NSW 2065
Australia

Where to go for further information

Pharmaceutical companies are not in a position to give people an individual diagnosis or medical advice. Your doctor or pharmacist is the best person to give you advice on the treatment of your condition. You may also be able to find general information about your disease and its treatment from books, for example in public libraries.

This leaflet was prepared on 20 October 2009.

The information provided applies only to: Imigran FDT tablets.

Imigran FDT is a registered trade mark of Aspen Global Incorporated.

  • Imigran FDT tablets, Sumatriptan (as succinate) 100 mg: AUST R 106715
  • Imigran FDT tablets, Sumatriptan (as succinate) 50 mg: AUST R 106714

©2003 Aspen Global Incorporated.

Version 2.0

BRAND INFORMATION

Brand name

Imigran FDT (Fast disintegrating tablets)

Active ingredient

Sumatriptan

Schedule

S4

 

1 Name of Medicine

Sumatriptan.

6.7 Physicochemical Properties

The chemical name of sumatriptan is 3-[2-(dimethylamino)ethyl]-N-methyl-1H-indole-5-methane sulphonamide. The molecular formula of sumatriptan is C14H21N3O2S, the relative molecular mass is 295.4. It takes the form of a white to pale yellow powder.
Chemically, sumatriptan succinate is: 3-[2-(dimethylamino) ethyl]-N-methyl-1H-indole-5methane sulphonamide, butane-1,4-dioate (1:1). The molecular formula of sumatriptan succinate is C14H21N3O2SC4H6O4, the relative molecular mass is 413.5. It takes the form of a white to off-white powder.

Chemical structure.


CAS number.

103628-48-4.

2 Qualitative and Quantitative Composition

Sumatriptan is the therapeutically active ingredient in Imigran nasal spray and sumatriptan succinate is the therapeutically active ingredient in Imigran tablets and injection.

Excipients with known effect.

Imigran 50 mg and 100 mg tablets contain sugars (as lactose).

Imigran tablets 50 mg.

Each tablet contains 50 mg sumatriptan base as the succinate salt.
The tablets also contain: lactose, lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, Opadry YS-1-1441-G.

Imigran tablets 100 mg.

Each tablet contains 100 mg sumatriptan base as the succinate salt.
The tablets also contain: lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, Opadry white OY-S-7393.

Imigran FDT 50 mg.

Each tablet contains 50 mg sumatriptan base as the succinate salt.
Imigran FDT also contains: calcium hydrogen phosphate anhydrous, microcrystalline cellulose, sodium bicarbonate, croscarmellose sodium, magnesium stearate and Opadry YS1-1441-G.

Imigran FDT 100 mg.

Each tablet contains 100 mg sumatriptan base as the succinate salt.
Imigran FDT also contains: calcium hydrogen phosphate anhydrous, microcrystalline cellulose, sodium bicarbonate, croscarmellose sodium, magnesium stearate and Opadry white OY-S-7322.

Injection.

Imigran MK II injection is available in pre-filled syringes containing 6 mg of sumatriptan base as the succinate salt, in an isotonic solution containing sodium chloride and water for injections (total volume 0.5 mL).

Imigran nasal spray.

Each nasal spray is a single dose unit of sumatriptan base in 0.1 mL aqueous solution containing sulfuric acid, monobasic potassium phosphate, dibasic anhydrous sodium phosphate, sodium hydroxide and purified water. The pH of the nasal spray solution is 5.5.

3 Pharmaceutical Form

Tablets.

Sumatriptan tablets are presented in two formulations: Imigran tablets and Imigran FDT tablets.
Imigran tablets are available in two strengths, 100 mg and 50 mg.
Imigran brand tablets 100 mg are white to off-white, film-coated, capsule shaped biconvex tablets engraved '100' on one face and plain on the other face.
Imigran brand tablets 50 mg are pink, film-coated, capsule-shaped biconvex tablets engraved '50' on one face and plain on the other face.
Imigran FDT tablets are available in two strengths, 100 mg and 50 mg.
Imigran FDT 100 mg are white film coated, triangular shaped, biconvex tablets debossed with 'GS YE7' on one face and '100' on the other.
Imigran FDT 50 mg are pink film coated, triangular shaped, biconvex tablets debossed with 'GS 1YM' on one face and '50' on the other.

Injection.

Imigran Mk II injection solution is a clear colourless to pale yellow liquid practically free from particles.

Nasal spray.

Two strengths of nasal spray are available: Imigran S nasal spray 10 mg and Imigran nasal spray 20 mg. The nasal spray solution is a clear pale yellow to dark yellow liquid.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Sumatriptan has been demonstrated to be a specific vascular 5-hydroxytryptamine-1 (5HT1) receptor agonist with no effect at other 5HT receptor (5HT2-5HT7) subtypes. The vascular 5HT1 receptor is found predominantly in cranial blood vessels and mediates vasoconstriction. In animals, sumatriptan selectively constricts the carotid arterial circulation, but does not alter cerebral blood flow. The carotid arterial circulation supplies blood to the extracranial and intracranial tissues, such as the meninges, and dilatation and/ or oedema formation in these vessels is thought to be the underlying mechanism of migraine in man. In addition, experimental evidence suggests that sumatriptan inhibits trigeminal nerve activity. Both these actions may contribute to the antimigraine action of sumatriptan in humans.

Clinical trials.

Clinical studies conducted in the adult population.

Table 4 shows 1 and 2 hour efficacy results for two placebo controlled trials of sumatriptan injection in 1104 adult migraineurs with moderate or severe migraine pain.
Table 5 demonstrates 2 and 4 hour efficacy results in two placebo controlled studies of sumatriptan tablets in 332 adult migraineurs experiencing moderate or severe pain.
Table 6 shows primary efficacy results at 2 hours for 5 placebo controlled trials of sumatriptan nasal spray in 2547 adult migraineurs experiencing moderate or severe pain.
Patients who had a history of migraine, with or without aura, and experienced between one and six attacks per month of severe/ moderately severe migraine during the previous 12 months were entered in the nasal spray studies. The following categories were not selected for the clinical studies: age < 18 years or > 65 years, history of nonmigraine headaches (i.e. tension type headache), cardiovascular disease (i.e. ischaemic heart disease, coronary vasospasm, atherosclerotic disease, diastolic blood pressure > 95 mmHg and systolic blood pressure > 160 mmHg), pregnancy and breastfeeding, females unless adequate contraception was employed, concurrent medication (ergotamine or dihydroergotamine, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, or lithium), history of substance abuse (alcohol, opiates or ergotamine), hypersensitivity or prior exposure to sumatriptan nasal spray or intranasal dihydroergotamine.
Specific studies involving asthmatic patients have not been conducted however a few asthmatic patients were included in the clinical trials.

Clinical studies conducted in the adolescent population.

Table 7 shows 60 and 120 minute efficacy results for sumatriptan nasal spray 10 mg and 20 mg in a placebo controlled study in adolescent migraineurs experiencing moderate or severe migraine pain.
Both sumatriptan nasal spray 10 mg and 20 mg were statistically superior to placebo at 60 minutes for headache relief, but 20 mg has the best overall efficacy profile for the acute treatment of migraine in adolescents compared with placebo.
Sumatriptan nasal spray 20 mg was shown to be associated with a number of secondary benefits, including headache free rates; and relieving migraine associated symptoms of photophobia at 120 minutes (p = 0.025) and phonophobia at 30, 60 and 120 minutes (p = 0.032, 0.023 and 0.001 respectively). No statistically significant differences were found with nausea or vomiting.

5.2 Pharmacokinetic Properties

Following subcutaneous injection, sumatriptan has a high mean bioavailability (96%) with peak serum concentrations occurring in 25 minutes. Average peak serum concentration after a 6 mg subcutaneous dose is 72 nanogram/mL. The elimination phase half-life is approximately 2 hours. After oral administration, sumatriptan is rapidly absorbed, 70% of maximum concentration occurring at 45 minutes. After a 100 mg dose the mean maximum plasma concentration is 54 nanogram/mL. Mean absolute oral bioavailability is 14% partly due to presystemic metabolism and partly due to incomplete absorption. Oral absorption of sumatriptan is not significantly affected by food.
Imigran FDT tablets and Imigran tablets have been established to be bioequivalent in the fasted state. In the fasted state, sumatriptan tmax was, on average, 10-15 minutes earlier for Imigran FDT relative to Imigran tablets. Imigran FDT after a high fat meal resulted in an average 12% increase in AUC(0-∞) and 15% increase in Cmax relative to Imigran FDT in the fasted state. AUC(0-2) was estimated to be an average of only 5% lower and tmax delayed by only 6.5 minutes for Imigran FDT in the fed, relative to the fasted state. These variations are not considered to be of clinical significance.
After intranasal administration, sumatriptan is rapidly absorbed, maximum plasma concentration occurring in 1-1.5 hours. After a 20 mg dose, the mean maximum concentration is 12.9 nanogram/mL. Mean intranasal bioavailability, relative to subcutaneous administration, is 15.8%, partly due to presystemic metabolism. Plasma protein binding is low (14-21%), mean volume of distribution is 170 L. Mean total plasma clearance is approximately 1160 mL/min and the mean renal plasma clearance is approximately 260 mL/min.
A pharmacokinetic study in adolescent subjects (12-17 years) indicated that the mean maximum plasma concentration was 13.9 nanogram/mL and mean elimination half-life was approximately 2 hours following a 20 mg intranasal dose. Population pharmacokinetic modelling indicated that clearance and volume of distribution both increase with body size in the adolescent population resulting in higher exposure in lower bodyweight adolescents. The model predicted that a subject with a bodyweight of 40 kg would have an apparent clearance of 222 L/h and a volume of distribution of 850 L whilst the corresponding figures for a body weight of 66 kg would be 366 L/h and 1204 L. The predicted dependence of these parameters on body size should not pose any significant safety concern as the recommended initial dose range is 10-20 mg.
Nonrenal clearance accounts for about 80% of the total clearance. Sumatriptan is eliminated primarily by oxidative metabolism mediated by monoamine oxidase A. The major metabolite, the indole acetic acid analogue of sumatriptan, is mainly excreted in the urine, where it is present as a free acid and the glucuronide conjugate. It has no known 5HT1 or 5HT2 activity. Minor metabolites have not been identified. The pharmacokinetics of oral or intranasal sumatriptan do not appear to be significantly affected by migraine attacks.
In a pilot study no significant differences were found in the pharmacokinetic parameters between elderly and young healthy volunteers.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

4 Clinical Particulars

4.1 Therapeutic Indications

Imigran tablets, injection and nasal spray are indicated for the acute relief of migraine attacks with or without aura.
Imigran injection is also indicated for the acute treatment of cluster headaches.
There is no information available on the use of Imigran in the treatment of basilar or hemiplegic migraine.

4.3 Contraindications

Imigran should not be used in patients who have:
Hypersensitivity to any component of the preparation (see Section 2 Qualitative and Quantitative Composition).
A history of myocardial infarction.
Peripheral vascular disease or symptoms or signs consistent with ischaemic heart disease.
Prinzmetal's angina/ coronary vasospasm.
Uncontrolled hypertension.
Cerebrovascular accident or transient ischaemic attack.
Severe hepatic impairment.
Imigran should not be used within 24 hours of treatment with an ergotamine containing or ergot type medication, such as dihydroergotamine or methysergide.
Imigran should not be given to patients receiving monoamine oxidase inhibitors (MAOIs) or within two weeks of discontinuation of MAOI therapy.
Imigran should not be administered to patients with hemiplegic, basilar or ophthalmoplegic migraine.

4.4 Special Warnings and Precautions for Use

Imigran should only be used where there is a clear diagnosis of migraine. However, if a patient does not respond to the first dose, the opportunity should be taken to review the diagnosis before a second dose is given. The recommended doses of Imigran should not be exceeded.

Drowsiness.

Drowsiness may occur as a result of migraine or its treatment with Imigran. Caution is recommended in patients performing skilled tasks, e.g. driving or operating machinery.

Use in hepatic or renal impairment.

Imigran should also be administered with caution to patients with diseases which may affect significantly the metabolism, absorption and excretion of the drug, such as impaired hepatic or renal function. Studies have shown reduced sumatriptan clearance in patients with hepatic impairment. Lower doses should be considered in these patients. If appropriate, the first dose should be given under supervision to these patients.

Hypersensitivity to sulphonamides.

Patients with known hypersensitivity to sulphonamides may exhibit an allergic reaction following administration of Imigran. Reactions may range from cutaneous hypersensitivity to anaphylaxis. Evidence of cross sensitivity is limited, however, caution should be exercised before using sumatriptan in these patients.

Use in patients with asthma.

It is theoretically possible that asthmatic patients may react to nasal spray formulations; It is recommended that the physicians consider the benefit/ risk ratio of using this formulation in this group of patients.

Latex or rubber allergy.

Physicians should alert patients with a history of latex or rubber allergy that the unit dose vial within the nasal spray device is sealed with a rubber stopper.
The needle shield of the pre-filled syringe may contain dry natural latex rubber that has the potential to cause allergic reactions in latex sensitive individuals.
Patients should be advised to pay strict attention to the instruction leaflet for sumatriptan injection, especially regarding the safe disposal of needles and syringes. Needles and syringes may be hazardous and should be disposed of safely and hygienically.

Overuse.

Overuse of acute migraine treatments has been associated with the exacerbation of headache (medication overuse headache (MOH)) in susceptible patients. Withdrawal of the treatment may be necessary.

Co-administration with 5-HT1 agonists.

Coadministration of sumatriptan within 24 hours of other 5HT1-agonists is not recommended due to the potential for vasoconstrictive effects.

Cardiovascular precautions.

It is strongly recommended that sumatriptan not be given to patients in whom risk factors indicate a possibility of unrecognised coronary artery disease (CAD) unless a cardiovascular evaluation provides satisfactory clinical evidence that the patient is reasonably free of coronary artery and ischaemic myocardial disease or other significant underlying cardiovascular disease. The risk factors include hypertension, hypercholesterolaemia, smoker, obesity, diabetes, strong family history of CAD, female with surgical or physiological menopause, or male over 40 years of age. The sensitivity of cardiac diagnostic procedures to detect cardiovascular disease or predisposition to coronary artery vasospasm is modest, at best, and in extremely rare cases (less than 1 in 10,000), serious cardiac events have occurred in patients without underlying cardiovascular disease. If, during the cardiovascular evaluation, the patient's medical history of electrocardiographic investigations reveal findings indicative of, or consistent with coronary artery vasospasm or myocardial ischaemia, sumatriptan should not be administered (see Section 4.3 Contraindications).
Imigran may cause short lived elevation of blood pressure and peripheral vascular resistance. Sumatriptan should therefore be administered with caution to patients with controlled hypertension. Transient increases in blood pressure and peripheral vascular resistance have been observed in a small proportion of patients.
Serious cardiac events, including some that have been fatal, have occurred within a few hours following the use of Imigran injection or tablets. These events are extremely rare (less than 1 in 10,000) and the majority of these case reports were confounded by patients having pre-existing heart disease or risk factors for ischaemic heart disease and may reflect underlying disease and spontaneous events. Under these circumstances the specific contribution of Imigran cannot be determined. Events reported have included coronary artery vasospasm, transient myocardial ischaemia, myocardial infarction and cardiac arrhythmias including ventricular tachycardia and ventricular fibrillation. Therefore, Imigran should not be given to patients in whom unrecognised cardiac disease is likely without a prior evaluation for underlying cardiovascular disease. Such patients include postmenopausal women, males over 40 and patients with risk factors for coronary artery disease. Significant cardiovascular sequelae have been reported in patients in whom risk factors were not readily identifiable. There is no experience in patients with recent cardiac arrhythmias (especially tachycardias). Until further information is available, the use of Imigran is not recommended in these patients.
A myocardial infarct has been reported in a 14 year old male following the use of oral sumatriptan; clinical signs occurred within 1 day of drug administration.
When given intravenously Imigran can cause angina in susceptible patients. Imigran injection should therefore not be given intravenously.
Following administration, Imigran can be associated with transient symptoms, including chest pain and tightness, which may be intense and involve the throat. If symptoms consistent with ischaemic heart disease occur, appropriate investigations should be carried out and further doses should not be given until the results of these investigations are known. Patients should be advised to contact their doctor immediately if they experience symptoms consistent with ischaemic heart disease (see Section 4.3 Contraindications).

Cerebrovascular precautions.

Cerebral haemorrhage, subarachnoid haemorrhage, stroke and other cerebrovascular events have been reported in patients treated with oral or subcutaneous sumatriptan, and some have resulted in fatalities. The relationship of sumatriptan to these events is uncertain. In a number of cases, it appears possible that the cerebrovascular events were primary, sumatriptan having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine when they were not. Sumatriptan should not be administered if the headache being experienced is atypical of the patient. It should be noted that patients with migraine may be at increased risk of certain cerebrovascular events (e.g. cerebrovascular accident, transient ischaemia attack).
Before treating headaches in patients not previously diagnosed as migraineurs, and in migraineurs who present with atypical symptoms, care should be taken to exclude other potentially serious neurological conditions.
Imigran should be used with caution in patients with a history of seizures or other risk factors which lower the seizure threshold.
There is no experience in patients with recent cerebrovascular accidents. Until further information is available, the use of Imigran is not recommended in these patients (see Section 4.3 Contraindications).
There is no information available on the use of Imigran in the treatment of ophthalmoplegic migraine.

Other vasospastic events.

Sumatriptan may cause vasospastic reactions other than coronary artery vasospasm. Both peripheral vascular ischaemia and colonic ischaemia with abdominal pain and bloody diarrhoea have been reported.

Use in adolescents (12-17 years).

The efficacy of oral sumatriptan has not been established in placebo controlled trials carried out in 794 adolescent migraineurs. High placebo responses were found in these studies and there was a lack of statistically significant difference between placebo and oral doses ranging from 25 to 100 mg. The safety profile of oral and intranasal sumatriptan is similar to that of adults.

Paediatric use.

The safety and effectiveness of sumatriptan in children under the age of 12 years has not been established.

Use in the elderly.

Experience of the use of Imigran in patients aged over 65 is limited. However the pharmacokinetics do not differ significantly from a younger population. Until further clinical data are available, the use of Imigran in patients aged over 65 is not recommended.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Pharmacodynamic.

Prolonged vasospastic reactions have been reported with ergotamine. As these effects may be additive, concomitant use of ergotamine or ergotamine derivatives and Imigran should be avoided. Twenty four hours should elapse before Imigran is taken following any ergotamine containing preparation. Conversely, ergotamine containing preparations should not be taken until 6 hours have elapsed following Imigran administration (see Section 4.3 Contraindications).

Pharmacokinetic.

An interaction may occur between sumatriptan and MAOIs, and concomitant administration is contraindicated (see Section 4.3 Contraindications). Rarely an interaction may occur between sumatriptan and selective serotonin reuptake inhibitors. There have been rare post-marketing reports describing patients with serotonin syndrome (including altered mental status, autonomic instability, neuromuscular abnormalities, weakness, hyper-reflexia and incoordination) following the use of an SSRI. Serotonin syndrome has been reported following concomitant treatment with triptans and serotonin noradrenaline reuptake inhibitors (SNRIs).
If concomitant treatment with sumatriptan and an SSRI/ SNRI is clinically warranted, appropriate observation of the patient is advised.
The concomitant administration of any triptan/ 5-HT1-agonist with sumatriptan is not recommended.
There is no evidence of interactions with propranolol, flunarizine, pizotifen or alcohol.
Although there is no clear evidence, it is possible that an interaction may occur between serotonin 5HT1-agonists and the herbal remedy St John's wort (Hypericum perforatum), which may result in an increase in side effects.

Ophthalmic.

Intermittent transient changes on the surface of the cornea have been observed in toxicology studies in dogs. No causative mechanism has been established for these changes but there is no evidence to suggest that this is relevant to clinical exposure.
In studies carried out to test for local and ocular irritancy following administration of sumatriptan nasal spray, there was no irritancy seen in laboratory animals and no ocular irritancy observed when the spray was applied directly to the eyes of rabbits.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B3)
No obvious teratogenic effects have been seen in rats given oral doses of 500 mg/kg and intravenous doses up to 12.5 mg/kg or in rabbits given oral doses up to 100 mg/kg and intravenous doses up to 8 mg/kg during organogenesis (although it is noted that the number of pregnant rabbits investigated was limited).
Reproduction studies in rats have not revealed any clear evidence of impaired fertility (oral doses up to 500 mg/kg, subcutaneous doses up to 60 mg/kg, given before and during mating) or of impaired post-natal pup development (oral doses up to 1000 mg/kg, subcutaneous doses up to 81 mg/kg, given during the peri and post-natal period). In the rabbit, embryotoxicity cannot be ruled out. After oral administration, at doses of 5, 25 and 100 mg/kg on days 8-20 of gestation (severe maternal toxicity at 100 mg/kg) there was evidence of a small, increasing dose related trend in post-implantation intrauterine death with a similar, and significant trend being recorded after intravenous treatment (0.5 to 8 mg/kg, days 8-20 of gestation).
Term foetuses from Dutch Stride rabbits treated during the period of organogenesis with oral sumatriptan exhibited an increased incidence of cervicothoracic vascular defects and skeletal abnormalities.
When administered to pregnant rabbits throughout the period of organogenesis sumatriptan has occasionally caused embryolethality at doses which were sufficiently high to produce maternal toxicity.
Administration of this drug should only be considered if the expected benefit to the mother is greater than any possible risk to the foetus.
Sumatriptan is excreted in breast milk in animals. In rats given oral sumatriptan at 1000 mg/kg during the lactation period, 3 dams out of 20 showed total litter loss whilst in another litter, only 9/15 survived to the end of nursing. It has been demonstrated that following subcutaneous administration sumatriptan is excreted into breast milk. Infant exposure can be minimised by avoiding breastfeeding for 24 hours after treatment. Caution should be exercised when considering the administration of sumatriptan to a breastfeeding woman.

4.8 Adverse Effects (Undesirable Effects)

The most common side effect associated with treatment with Imigran administered subcutaneously is transient pain at the site of injection; stinging/ burning, swelling, erythema, bruising and bleeding at the injection site have also been reported.
The most common side effects associated with treatment with Imigran are:
Pain, sensations of tingling, heat or cold, heaviness, pressure or tightness. These are usually transient, and may be intense and can affect any part of the body, including the chest and throat.
Flushing, dizziness and feelings of weakness. These are mostly mild to moderate in intensity and transient.
Fatigue, drowsiness, sensory disturbance including paraesthesia and hypoaesthesia have been reported.
Nausea and vomiting occurred in some patients, but the relationship to Imigran is not clear.
Transient increases in blood pressure arising soon after treatment have been recorded.
Dyspnoea.
Following administration of Imigran nasal spray, mild transient irritation or burning sensation in the nose or throat, or epistaxis, have been reported.
Although direct comparisons are not available, nausea, vomiting and fatigue appear to be less frequent with subcutaneous administration of Imigran than with tablets. Conversely, flushing, paraesthesia and sensations of tingling, heat or cold, pressure and heaviness may be more common after the injection.
Serious coronary events have been reported (see Section 4.4 Special Warnings and Precautions for Use). Other cardiovascular adverse reactions include hypotension, bradycardia, tachycardia and palpitations. Very rarely (less than 1 in 10,000) Raynaud's phenomenon, angina and ischaemic colitis have been reported.
There have been rare (less than 1 in 1,000) reports of seizures following migraine attacks treated with sumatriptan. Although some have occurred in patients with either a history of seizures or concurrent conditions predisposing to seizures there are also reports in patients where no such predisposing factors are apparent.
Patients treated with Imigran very rarely (less than 1 in 10,000) exhibit visual disorders like flickering and diplopia. Additionally, cases of nystagmus, scotoma and reduced vision have been observed. Very rarely loss of vision has occurred, which is usually transient. However, visual disorders may also occur during a migraine attack itself.
Hypersensitivity reactions ranging from cutaneous hypersensitivity (e.g. rash, urticaria, pruritus or erythema) to, in rare (less than 1 in 10,000) cases, anaphylaxis have been recorded (see Section 4.4 Special Warnings and Precautions for Use).
Minor disturbances of liver function tests have occasionally been observed. There is no evidence that clinically significant abnormalities occurred more frequently than with placebo.
In the clinical trial programme, decreased lymphocyte count post-treatment was observed in a number of patients receiving either oral or subcutaneous Imigran. This effect was not dose related and was also observed in patients receiving placebo. The significance of these findings is uncertain.
In the clinical trial programme, a similar profile of clinical adverse events was reported in the adolescent and adult populations taking Imigran tablets or nasal spray.
In four bioequivalence studies, the safety profile for Imigran FDT was similar to that observed for Imigran tablets.

Post-marketing data.

In addition to the drug related adverse reactions reported from clinical trials, the following serious spontaneous events, reported to be possibly, probably or almost certainly caused following use of either subcutaneous, oral or intranasal sumatriptan in patients less than 18 years of age have been identified.

Cardiovascular.

Myocardial infarction.

Cerebrovascular.

Cerebellar infarction.

Neurology.

Seizures, tremor and dystonia.

Nonsite specific.

Anaphylaxis.

Skin.

Urticaria, rash.
See Tables 1, 2 and 3.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

Imigran is indicated for the acute intermittent relief of both migraine and cluster headache. It should not be used prophylactically.
Ergotamine or ergotamine derivatives and Imigran should not be administered concurrently (see Section 4.3 Contraindications).

Injection.

Imigran injection should be injected subcutaneously using an autoinjector. Patients should be advised to observe strictly the instruction leaflet for the Imigran autoinjector, especially regarding the safe disposal of syringes and needles.
The first dose of Imigran injection should be given by, or under the direct supervision of, a physician. As with the administration of the first dose of any injectable therapeutic product, appropriate resuscitative equipment should be available. Appropriate advice on the future use of the autoinjector by the patient should also be given at this time. The physician should ensure that the patient is familiar with and understands the Consumer Medicine Information.

Migraine.

It is recommended to start the treatment at the first sign of a migraine headache or associated symptoms, such as nausea, vomiting or photophobia. The efficacy of sumatriptan is independent of the duration of the attack when starting treatment. Administration during a migraine aura, prior to other symptoms occurring, may not prevent the development of a headache.
If a patient does not respond to the first dose of Imigran, a second dose should not be taken for the same attack. Imigran may be used for subsequent attacks.

Injection.

The recommended adult dose of Imigran is a single 6 mg, subcutaneous injection. If symptoms recur, a further subcutaneous dose of 6 mg may be given at any time in the next 24 hours provided that one hour has elapsed since the first dose. The maximum dose in 24 hours is 2 x 6 mg injections (12 mg).

Tablets.

The initial recommended adult dose of oral Imigran is 50 mg. Some patients may require 100 mg. The dose should be adjusted according to the individual's response. If symptoms recur, further doses may be given in the next 24 hours provided not more than 300 mg is taken in any 24 hour period. The tablet should be swallowed whole with water.

Nasal spray.

Imigran nasal spray is particularly suitable for patients who suffer with nausea and vomiting or who require a rapid onset of effect during an attack.

Adults.

The optimal dose of Imigran nasal spray is 20 mg, administered into one nostril. For some patients 10 mg may be effective.

Adolescents (12-17 years).

The recommended dose of Imigran nasal spray is 10 mg-20 mg (see Section 5.1 Pharmacodynamic Properties, Clinical trials), with consideration given to the patient's bodyweight and patient variability of migraine attacks. The dose of Imigran nasal spray should be administered into one nostril.
If symptoms recur a second dose may be given in the next 24 hours, provided that there is a minimum interval of two hours between the two doses. Not more than 40 mg of nasal spray should be used in any 24 hour period.

Cluster headache.

The recommended adult dose is a single 6 mg subcutaneous injection for each cluster attack. The maximum dose in 24 hours is two 6 mg injections (12 mg) providing at least one hour has elapsed between injections.

4.7 Effects on Ability to Drive and Use Machines

No studies on the effects on the ability to drive and use machines have been performed. Drowsiness may occur as a result of migraine or its treatment with sumatriptan. This may influence the ability to drive and to operate machinery.

4.9 Overdose

There have been some reports of overdosage with Imigran injection. Patients have received single injections of up to 12 mg subcutaneously without significant adverse effects. Single doses up to 40 mg intranasally, up to 16 mg subcutaneously and up to 400 mg with Imigran tablets orally were not associated with side effects other than those mentioned. There is no experience of doses greater than these.
If overdosage with Imigran occurs, the patient should be monitored for at least ten hours and standard supportive treatment applied as required.
It is unknown what effect haemodialysis or peritoneal dialysis has on the plasma concentrations of sumatriptan.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

See Section 2 Qualitative and Quantitative Composition.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Tablets.

Store below 30°C.

Injection.

Store below 30°C. Protect from light.

Nasal spray.

Store below 30°C. Protect from light.

6.5 Nature and Contents of Container

Imigran tablets 100 mg are available in packs containing 2 and 6 tablets in aluminium foil blisters.
Imigran tablets 50 mg are available in packs containing 2, 4 and 12 tablets in aluminium foil blisters.
Imigran FDT 50 mg and Imigran FDT 100 mg are available in packs containing 2, 4, 6, 12 and 18 tablets in aluminium foil blisters.
The nasal spray solution is supplied in Type I glass vials sealed with chlorobutyl rubber stoppers. The stoppered vial is assembled into a unit dose nasal spray device.
Packs contain 2 individual nasal sprays each in a blister pack with an integral actuator.
Imigran Mk II injection is available in an autoinjector kit containing two pre-filled syringes and one autoinjector; and in refill packs of two pre-filled syringes. The injection is supplied in Type I glass clear syringes sealed with chlorobutyl rubber plunger stoppers.
Not all strengths, dose forms, pack sizes, container types are being distributed in Australia.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

Summary Table of Changes